Key role of estrogens and endothelial estrogen receptor alpha in blood flow-mediated remodeling of resistance arteries

TitreKey role of estrogens and endothelial estrogen receptor alpha in blood flow-mediated remodeling of resistance arteries
Type de publicationArticle de revue
AuteurTarhouni, K., Guihot, Anne-Laure , Freidja, M. L, Toutain, Bertrand, Henrion, B., Baufreton, Christophe , Pinaud, F., Procaccio, Vincent , Grimaud, Linda , Ayer, Audrey, Loufrani, Laurent , Lenfant, Françoise, Arnal, Jean-François, Henrion, Daniel
EditeurAmerican Heart Association
TypeArticle scientifique dans une revue à comité de lecture
Pagination605 - 11
Titre de la revueArteriosclerosis, thrombosis, and vascular biology
Mots-clésAnimals, Blood Pressure/drug effects, Caveolin 1/metabolism, Endothelial Cells/drug effects/metabolism, Estradiol/administration & dosage, Estrogen Receptor alpha/agonists/deficiency/genetics, Estrogen Receptor beta/deficiency/genetics, Estrogen Replacement Therapy, Female, Mesenteric Arteries/drug effects/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type III/deficiency/genetics, Nitric Oxide/metabolism, Ovariectomy, Phosphorylation, Rats, Rats, Wistar, Regional Blood Flow/drug effects, Splanchnic Circulation/drug effects, Time Factors, Vascular Resistance/drug effects, Vasodilation/drug effects
Résumé en anglais

OBJECTIVE: Flow- (shear stress-)mediated outward remodeling of resistance arteries is involved in collateral growth during postischemic revascularization. As this remodeling is especially important during pregnancy, we hypothesized that estrogens may be involved. A surgical model eliciting a local increase in blood flow in 1 mesenteric resistance artery was used in 3-month-old ovariectomized female rats either treated with 17-beta-estradiol (E2) or left untreated. METHODS AND RESULTS: After 14 days, arterial diameter was greater in high-flow arteries than in normal-flow vessels. An ovariectomy suppressed high-flow remodeling, while E2 restored it. High-flow remodeling was absent in mice lacking the estrogen receptor alpha but not estrogen receptor beta. The kinetics of inflammatory marker expression, macrophage infiltration, oxidative stress, and metaloproteinases expression were not altered by the absence of E2 after 2 and 4 days, that is, during remodeling. Nevertheless, E2 was required for the increase in endothelial nitric oxide synthase expression and activation at day 4 when diameter expansion occurs. Finally, the impact of E2 on the endothelium appeared crucial for high-flow remodeling, as this E2 action was abrogated in mice lacking endothelial NOS, as well as in Tie2-Cre(+) ERalpha(f/f) mice. CONCLUSIONS: We demonstrate the essential role of E2 and endothelial estrogen receptor alpha in flow-mediated remodeling of resistance arteries in vivo.

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Titre abrégéArterioscler Thromb Vasc Biol